Oral cancer is the sixth most common cancer worldwide and over two thirds of cases occur in developing countries. In India, it is the most common cancer in men and the third most common in women. Only half of oral cancer patients live 5 years, even less of those with advanced stage disease survive. Advances in early detection and diagnosis would greatly improve survival and decrease suffering from oral cancer. Optical based diagnostic aids are promising new technologies to improve detection of epithelial malignancies. During carcinogenesis, the optical properties of tissue are altered and these changes can be used to non-invasively distinguish normal from neoplastic mucosa. The objective of this international collaborative project, which builds upon previous NIH funded work, is to determine whether new optical imaging technology, fluorescence and reflectance imaging and spectroscopy, can facilitate early detection and diagnosis of oral neoplasia in a high risk population in India. Our first Aim is to determine whether multispectral imaging and spectroscopy can improve screening and diagnosis of potentially malignant oral lesions in a high risk population in India. We will obtain wide-field autofluorescence and reflectance images of oral premalignant lesions (OPLs) in 90 patients who are recruited for oral cancer screening trials at the Tata Memorial Hospital in Mumbai India. These images will be compared to findings using standard white light (WL) illumination. At the same time, an in depth, focal interrogation from several sites using fluorescence and reflectance spectra will be performed. Clinical diagnoses using standard white light, clinical diagnoses using multispectral imaging, spectroscopy data, and cytology and histopathology diagnoses will be compared to determine the positive and negative predictive value of using the device. In Aim 2, we will determine whether this technology can improve screening and diagnosis in an Indian population with high risk for oral cancer but no clinically visible lesions using similar methodology. In Aim 3, we evaluate the correlation of presence of genetic damage (such as aneuploidy and loss of heterozygosity) and morphologic changes (hyperkeratosis, inflammation, dysplasia) to altered optical signatures. Successful completion of this project will determine the diagnostic potential and applicability of this technology for oral cancer detection and diagnosis in communities with limited resources. 7. Project Narrative Oral cancer is the sixth most common cancer worldwide and over two thirds of cases occur in developing countries. In India, it is the most common cancer in men and the third most common in women. Only half of oral cancer patients live 5 years, even less of those with advanced stage disease survive. Advances in early detection and diagnosis would greatly improve survival and decrease suffering from oral cancer. Optical based diagnostic aids are promising new technologies to improve detection of epithelial malignancies. The objective of this international collaborative project, which builds upon previous NIH funded work, is to determine whether new optical imaging technology, fluorescence and reflectance imaging and spectroscopy, can facilitate early detection and diagnosis of oral neoplasia in a high risk population in India. We will determine whether multispectral imaging and spectroscopy can improve screening and diagnosis of potentially malignant oral lesions in a high risk population in India. We will compare optical data in 190 subjects who are recruited for oral cancer screening trials at the Tata Memorial Hospital in Mumbai India, to standard clinical diagnosis, histopathologic results, and molecular biomarker findings. Successful completion of this project will determine the diagnostic potential and applicability of this multispectral imaging and spectrsocpy technology for oral cancer detection and diagnosis in communities with limited resources.